Therapy of tacrolimus combined with corticosteroids in idiopathic membranous nephropathy

We evaluated the efficacy and safety of tacrolimus (TAC) combined with corticosteroids in treating patients with idiopathic membranous nephropathy (IMN). One hundred seventy-seven biopsy-proven IMN patients were recruited in this retrospective clinical study. Sixty patients received TAC (target blood concentration of 4–8 ng/mL) and 117 patients received daily cyclophosphamide (CYC, 100 mg) combined with prednisone. Remission rates at the end of the first, second and third month in the TAC group were significantly higher than that in the CYC group (1st: 35.0 vs 19.7%, P<0.05; 2nd: 56.7 vs 38.5%, P<0.05; 3rd: 76.7 vs 59.0%, P<0.05). In the first 3 months, daily urinary protein and serum albumin in the TAC group obtained a better improvement than that in the CYC group (P<0.05). At the end of the sixth and the twelfth month, the remission rates, daily urinary protein and serum albumin were all comparable between the two groups (P>0.05). No significant difference of relapse rate between the groups was found (16.3 vs 12.0%, P>0.05). Patients were more likely to develop glucose intolerance in the TAC group. The TAC regimen obtained more benefits in treating IMN patients, especially in the first 3 months, than the CYC regimen.

A meta‑analysis of bevacizumab combined with chemotherapy.

INTRODUCTION: Angiogenesis plays an important role in the biology of ovarian cancer. The clinical efficacy and side effects of bevacizumab, the vascular endothelial growth factor inhibitor, on survival and toxicity in women with this ovarian cancer, was not conclusive. We performed this systematic review and meta‑analysis in order to clarify the efficacy of bevacizumab combined with chemotherapy in the treatment of ovarian cancer. MATERIALS AND METHODS: We searched the electronic database of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CNKI for clinical controlled trials of comparing bevacizumab combined with chemotherapy and chemotherapy alone in the treatment of ovarian cancer. The primary outcomes of eligible studies included median progression‑free survival (PFS), overall survival (OS), and toxicities such as enterobrosis, hypertension, albuminuria, congestive heart failure (CHF), neutrophils, thrombosis, and bleeding. The Hazard ratio (HR) and relative risk were used for the meta‑analysis and were expressed with 95% confidence intervals (CIs). All the statistical analyses were carried out by Stata 11.0 software (http://www.stata.com; Stata Corporation, College Station, TX, USA). RESULTS: We included 5 studies with 1798 cases in the bevacizumab combined with the chemotherapy group and 1810 subjects in the chemotherapy alone group. The pooled results showed that bevacizumab + chemotherapy compared with chemotherapy alone can significant prolong the median PFS (HR, 0.64; 95% CI, 0.46–0.82; P < 0.05) but not the OS (HR, 0.84; 95% CI, 0.59–10.9; P > 0.05); the toxicity analysis showed that the enterobrosis, hypertension, albuminuria, neutrophils, thrombosis, and bleeding were significantly increased in the bevacizumab + chemotherapy group compared with chemotherapy alone (Pall < 0.05). But the CHF risk between the two groups was not statistical different (P > 0.05). CONCLUSION: Bevacizumab combined with chemotherapy prolonged the median PFS in patients with ovarian cancer but also increase the risk of developing enterobrosis, hypertension, albuminuria, neutrophils, thrombosis, and bleeding.

A Randomized Trial of Ligustrazini Hydrochlorioi in the Treatment of Viral Encephalitis in Children.

Introduction: Chuanxiong is a herb used in traditional Chinese medicine for the Treatment of viral encephalitis. In animal studies it has shown to inhibit the synthesis and activity of Thromboxane (TXA2) and abate the imbalance between Thromboxane (TXA2) and Prostacyclin (PGI2). As a result, cerebral edema, ischemia and hypoxia could be improved. The aim of this study is to evaluate its effect in the treatment of viral encephalitis in children. Methodology: Ninety-nine patients with viral encephalitis were randomly divided into two groups. Ligustrazini Hydrochlorioi (LH) consisting of 51 cases (males 30, females 21; age 5 years and nine month±8 years and 2month) was given LH 4mg/kg per day in 100- 300mls of 10% glucose and infused intravenously over a three to four hour period, for 7 days as a course of treatment. A control groups of 48 cases(males 31, females 17; age 5 years and three month±4 years and three month) received the conventional treatment of Vitamin C(2.0-3.0g), Coenzyme A(100u) and Adenosine Triphosphate(ATP)(40mg) in 100-300 mls of 10% glucose infused intravenously daily for 7 days. Results: The total response rate in the LH group and the control group were 94.12% and 68.75% respectively (u=3.271 p<0.05). The average time to improvement was 4.29±1.41 days and 7.31±2.66 days respectively. No adverse effect was observed in both groups. Conclusion: We conclude that LH is an effective, safe and well tolerated treatment for children encephalitis.

Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-á) on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-á (10 or 100 ng/mL) for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-á treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-á decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-á did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-á increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

Mechanism of the transforming growth factor-â induction of fibronectin expression in hepatic stem-like cells

Transforming growth factor-â1 (TGF-â1) plays an important role in the fibrogenic process in the liver. The aim of the present study was to explore the action of TGF-â1 on fibronectin expression in rat hepatic stem-like cells and the underlying mechanisms. The level of fibronectin expression was determined in hepatic stem-like cells (WB cells) before and after TGF-â1 stimulation by RT-PCR and Western blot methods. Using immunogold transmission electron microscopy and the Western blot method, we observed the result of the expression and the distribution of cAMP, phosphorylated Smad3 and Smad7 before and after TGF-â1 treatment. The levels of fibronectin expression in both mRNA and protein increased 4- to 5-fold after TGF-â1 stimulation, reaching an optimum level after 8 h and then gradually falling back. Similarly, TGF-â1 stimulation resulted in an increase of cAMP in WB cells, peaking at 8 h. After treatment with TGF-â1 for 24 h, the expression of cAMP gradually decreased. In addition, we found that TGF-â1 treatment also contributed to the increased expression and to changes in cellular distribution of phosphorylated Smad3 (translocation from the cytoplasm to the nucleus) and Smad7 (translocation from the nucleus to the cytoplasm) in WB cells. The present study demonstrates that TGF-â is involved in the fibrogenic process in hepatic stem cells through up-regulation of fibronectin expression, and the mechanisms underlying this process may be associated with the activation of cAMP and Smad pathways.